In vivo cardiac electrophysiology

Cardiac electrophysiological studies in vivo were performed to evaluate the propensity for ventricular arrhythmias in chronically epileptic (7‐12 months following pilocarpine induction) and age‐matched sham animals. To evaluate whether β‐adrenergic blockade was protective against ventricular arrhythmias in the epileptic compared to sham rats, a subset of animals was treated with atenolol (10 mg/kg/dose, ip)²⁶ or saline twice daily for 3 days prior to the studies (sham + vehicle = 13, sham + atenolol = 4, epileptic + vehicle = 17, epileptic + atenolol = 9). To investigate whether atenolol could reverse ECG abnormalities, a subset of animals (n = 3 for sham + vehicle, sham + atenolol, and epileptic + vehicle; n = 6 for epileptic + atenolol) underwent ECG recording prior to and following atenolol treatment. Animals were anesthetized using 2% isoflurane in 1 L/min O₂. A 6‐lead body‐surface ECG and 4 intracardiac electrograms were recorded using a computer‐based acquisition system (Emka Technologies). Animals’ body temperatures were maintained at 36°C using a heating pad. We measured HRV from the surface ECG recordings prior to the electrophysiological (EP) studies as an additional surrogate marker for cardiac autonomic control. Standard deviation of the NN intervals (SDNN) and square root of the mean squared differences of successive NN intervals (RMSSD) represented time domain variables. Frequency domain variables included low frequency (LF: 0.05–0.75 Hz) and high frequency (HF: 0.75–2.5 Hz).²⁴ Atrial and ventricular intracardiac electrograms were recorded using a 1.6F octopolar catheter (EPR‐802, Millar Instruments, Houston, TX) inserted into the right external jugular vein. Bipolar right atrial pacing and right ventricular pacing were performed using 2‐msec current pulses delivered by an external stimulator (STG‐3008; Multi Channel Systems, Reutlingen, Germany). To induce ventricular arrhythmias, programmed electrical stimulation was performed at cycle lengths of 100 msec for 8 beats followed by 1 extra‐stimulus (S₂) at shorter coupling intervals. Ventricular tachycardia was defined as a sequence of >3 spontaneous ventricular beats following program electrical stimulation. Each animal underwent 2 or 3 programmed electrical stimulation (PES) trials. An animal was considered susceptible to PES‐induced VT if 2 of the 3 trials resulted in VT.